# Modulation of sex steroid-induced female social behaviors in an animal model

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $442,781

## Abstract

ABSTRACT
Our long-term goal is to understand steroid regulation of social interaction by studying limbic-hypothalamic
neural circuits that control female sexually receptivity, lordosis. We demonstrated that within this circuit,
estradiol membrane-initiated signaling activates an arcuate nucleus (ARH) to medial preoptic nucleus
(MPN) projection responsible for transient μ-opioid receptor (MORs) activation needed for full sexual
receptivity. These MOR neurons in turn project to the ventromedial nucleus of the hypothalamus (VMH)
modulating lordosis behavior. The present proposal is based on these results and on results in male mice
that show that the posterodorsal medial amygdala (MeApd) modulates social behavior. Because in females,
MeApd projections affecting the social behavior, lordosis, are not well defined, we seek to characterize
specific MeApd projections that modulate the ARH-MPN-VMH circuit underlying steroid activation of female
sexual receptivity. We will test the general hypothesis that the MeApd gates estradiol-initiated opioid
inhibition to modulate sexual receptivity. Three Specific Aims are proposed to functionally dissect this
circuit: 1) Selective activation of intrinsic ARH NPY neurons, and MPN-projecting POMC terminals inhibit
lordosis. This experiment formally tests that the sequential activation of NPY and POMC neurons inhibits
lordosis. NPY-Cre and POMC-Cre neurons will be infected with a stimulatory Cre-dependent
channelrhodopsin (ChR2) adeno-associated virus (AAV) and photostimulated in behaving female mice. 2)
The MeApd differentially modulates sexual receptivity through glutamatergic projections to the MPN, and
GABAergic to the VMH. We will use AAV-directed expression of ChR2, to stimulate, or halorhodopsin, to
inhibit, glutamatergic and GABAergic MeApd outputs. Our expectation is that glutamatergic inputs to the
MPN enhance the MOR-mediated inhibition of lordosis (asocial behavior), while GABAergic inputs to the
VMH promote receptivity (social behavior), as measured by the lordosis response to stimulus males. 3)
Sexual receptivity involves a switch from glutamatergic to GABAergic neuron activation in the MeApd.
These experiments will determine if in females, as in males, the MeApd controls social behavior through
shift from glutamatergic (asocial) to GABAergic (social) outputs. First, we will determine the pattern of
glutamatergic and GABAergic neuron activation in the MeApd induced by estradiol, and estradiol +
progesterone is associated with the change from nonreceptive/asocial behavior to receptive/social behavior.
Finally, we will sequentially inhibit glutamatergic and GABAergic MeApd neurons in gonadally intact, cycling
vGLUT-Cre and vGAT-Cre mice using a Cre-dependent halorhodopsin-AAV. Together, these experiments
will provide a functional circuit analysis of how steroid signaling in the limbic-hypothalamic circuit leads a
prototypic social interaction, lordosis behavior.

## Key facts

- **NIH application ID:** 10359101
- **Project number:** 5R01HD098284-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** PAUL E MICEVYCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $442,781
- **Award type:** 5
- **Project period:** 2020-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359101

## Citation

> US National Institutes of Health, RePORTER application 10359101, Modulation of sex steroid-induced female social behaviors in an animal model (5R01HD098284-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10359101. Licensed CC0.

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